ANTIBIOTIC COATED COLLAGEN GRANULES VS
ANTIBIOTIC DRESSING IN CHRONIC ULCERS
A DISSERTATION SUBMITTED TO THE TAMILNADU
DR.M.G.R MEDICAL UNIVERSITY
CHENNAI
in partial fulfilment of the regulations for the award of degree of
M.S. DEGREE EXAMINATION
This is to certify that the dissertation entitled “COMPARATIVE STUDY
OF THE OUTCOME OF ANTIBIOTIC COATED COLLAGEN
GRANULES VS ANTIOBIOTIC DRESSING IN CHRONIC ULCERS” is
a bonafide research work done by Dr. MICHAEL SENRAJ J, M.S. Postgraduate
student in the Department of General Surgery, Madurai Medical College & Hospital,
Madurai, in partial fulfillment of the requirement for the degree of M.S. in GENERAL
SURGERY from May 2018 – May 2019.
Date:
Professor,
CERTIFICATE BY THE GUIDE
This is to certify that the dissertation entitled “COMPARATIVE STUDY OF
THE OUTCOME OF ANTIBIOTIC COATED COLLAGEN
GRANULES VS ANTIOBIOTIC DRESSING IN CHRONIC ULCERS” is
a bonafide research work done by Dr. MICHAEL SENRAJ J, M.S. Postgraduate
student in the Department of General Surgery, Madurai Medical College & Hospital,
Madurai, in partial fulfillment of the requirement for the degree of M.S. in
GENERAL SURGERY.
CERTIFICATE BY THE HEAD OF THE DEPARTMENT
This is to certify that the dissertation entitled “COMPARATIVE STUDY OF
THE OUTCOME OF ANTIBIOTIC COATED COLLAGEN
GRANULES VS ANTIOBIOTIC DRESSING IN CHRONIC ULCERS” is
a bonafide research work done by DR. MICHAEL SENRAJ J, M.S. Postgraduate
student in the Department of General Surgery, Madurai Medical College Madurai,
under the guidance of Dr.V.SELVARAJ M.S.,Dch., Professor, Department of
General Surgery, Madurai Medical College, GRH, Madurai in partial fulfillment of
the requirements for the degree of M.S. in GENERAL SURGERY.
Date:
Professor and HOD of General
Surgery, Department of General Surgery,
Madurai Medical College, Madurai
This is to certify that the dissertation entitled “COMPARATIVE STUDY
OF THE OUTCOME OF ANTIBIOTIC COATED COLLAGEN
GRANULES VS ANTIOBIOTIC DRESSING IN CHRONIC ULCERS” is a
bonafide research work done by Dr. MICHAEL SENRAJ J, Postgraduate student in
the Department of General Surgery, Madurai Medical College Madurai, under the
guidance of Dr.V.SELVARAJ M.S.,DCH., Professor, Department of General
Surgery, Madurai Medical College, GRH, Madurai in partial fulfillment of the
requirements for the degree of M.S. in GENERAL SURGERY.
Place : Madurai
STUDY OF THE OUTCOME OF ANTIBIOTIC COATED
COLLAGEN GRANULES VS ANTIOBIOTIC DRESSING IN
CHRONIC ULCERS” is a bonafide and genuine research work carried out by
me under the guidance of Dr.V.SELVRAJ M.S.,DCH Professor, Department of
General Surgery, Madurai Medical College, Madurai. The Tamil Nadu
Dr. M.G.R. Medical University, Chennai shall have the rights to preserve, use and
disseminate this dissertation in print or electronic format for academic/research
purpose.
Date:
Madurai.
ACKNOWLEDGEMENT
This study would have been impossible without the enduring guidance of
my eminent teacher and esteemed guide Dr.V.SELVARAJ MS.,DCH.,
Professor, Department of Surgery, Madurai Medical college. I would like to
express my sincere and heartfelt gratitude for his resolute guidance, precise
approach, constructive criticism and meticulous supervision throughout the
course of my work and preparation of manuscripts that have been a valuable part
of my learning experience.
I express my sincere gratitude to Dr.A. M. SYED IBRAHIM, M.S. FIAS,
Professor and Head, Department of Surgery, Madurai Medical College, Madurai,
for his valuable suggestion, indispensable guidance, critical appreciation, support
and affection in pursuit of this study and post-graduation.
Sincere and heartfelt thanks to all other esteemed teachers in the
Department of General Surgery of Madurai Medical College, Madurai.
I am also thankful to my Assistant Professors Dr.D.LATHA MS.,DA.,
Dr. C. SARAVANAN MS.,D.Ortho., Dr.S.THIRUMALAIKANNAN MS.,
DCH., Dr. C.RAJKUMAR MS.,MCH., Dr.S.MUTHUKUMAR MS., MCH.,
for their help.
I express my gratitude to all the patients involved in the study. Without
their co-operation the study would not have been possible. I would like to thank
my parents who stood by me in every step of the way and are a constant source of
inspiration.
Date:
Postgraduate in General Surgery,
Department of General Surgery,
3 Materials and Methods 5
4 Review of Literature 8
5 Results & Statistical Analysis 58
6 Discussion 68
7 Conclusion 70
8 References 71
Consent form 81
Wound Healing is a dynamic process involving soluble mediators, a
variety of cells, and extracellular matrix. Wound result from precise disruption
of tissue by the surgeon’s knife (incision) to widespread damage of tissue (e.g.
major trauma, burns). It also results from a contusion, hematoma, laceration or an
abrasion. The continuity of the skin must be restored expeditiously because it
plays a crucial role in maintaining homeostasis.
Wounds that are difficult to treat includes diabetic ulcers, venous ulcers,
trophic ulcers, pressure sores and necrotizing fasciitis. An ideal dressing used in
the wound management should be economical, easy to apply, readily available
that will provide good pain relief, protect wound from infection, promote healing,
keep moisture, be elastic, and non - antigenic and adhere well to the wound and
waiting for spontaneous epithelisation and healthy granulation tissue.
Among newer type of wound dressings - Biological Dressings Like
Collagen create the most physiological interface between the wound surface,
environment and impermeable to bacteria. Collagen, the most abundant protein in
the body, plays a critical role in the successful completion of adult wound healing.
Its deposition, maturation, and subsequent remodelling are essential to the
functional integrity of the wound.
Collagen granule dressing has better advantage over conventional dressing
in terms of collagen formation with greater reduction in inflammatory cells during
2
healing days resulting in decreased days of healing, whereas conventional
dressing has minimal collagen formation, high grade of inflammation during the
healing days with maximum exudates formation resulting in increased days of
healing. A collagen granule dressing has another advantage over conventional
dressing in terms of non- immunogenic, non- pyrogenic, being natural, easy
application, hypo allergic and pain free.
3
AIM OF THE STUDY
To compare the efficacy of antibiotic coated collagen granule dressings and
conventional antibiotic dressing in chronic wounds in terms of
- Reduced wound healing time,
Period of study : 1 year.
Selection of study : Patients presenting with the ulcers of duration
more than 6 weeks.
physical status and clinical profile.
Methods : Randomized
Chronic ulcers.
All non-healing chronic ulcers are included like diabetic ulcers, traumatic
ulcers, pressure sores, amputation stump ulcers, post-surgical wound gaping of
at least 6 weeks duration.
EXCLUSION CRITERIA
3. Patients with connective tissue disorders and immune system disorders.
4. Patients on immunosuppressive drugs, steroids, chemotherapy and
radiotherapy.
5. Patients with any known allergy to the dressing materials.
5
Patients presenting with chronic ulcers in GRH, Madurai OPD and
casualty will be selected in this study.
Following consent, a questionnaire will be filled to record the patient`s
demographic data, duration of disease and other treatment details.
This is a prospective study comprising of chronic ulcer patients.
Patients were categorised into 2 groups A (study group) and B (control
group).
Complete blood count, renal function tests, serum proteins and pus
culture and sensitivity will be sent.
All the patients will be started on empirical intravenous antibiotic and
changed after obtaining the culture report.
One group received collagen granule dressing and the other one received
the conventional antibiotic dressing with metronidazole and povidone
iodine-soaked gauzes.
In study group A after giving a saline wash collagen granules are applied
and the wound dressing done.
6
In control group after giving thorough wound wash antibiotic dressing is
done with povidone iodine and metronidazole.
Wound will be inspected after 3 days.
Wound surface area will be measured before and after the application of
collagen granules dressing and documented.
Wound surface area will be measured with the help of a paper with
multiple squares each having a surface area of 1 sq. cm.
Wound surface area will be noted down in the proforma.
Wounds will be assessed for:
- reduction in surface area
cover with grafting.
- reduced hospital stays.
Each box corresponds to 1 square cm.
Wound surface area will be measured before and after each dressing.
8
HISTORICAL BACKGROUND OF WOUND HEALING
• The treatment and healing of wounds are the oldest topics discussed
in the medical literature and probably earliest problems of human race.
• Early surgeons like Ambrose, Pare, John Hunter, & Sir James Paget
have given some scientific knowledge to their handling of wounds,
particularly those resulted from war.
• Halsted was intensely interested in wound healing process.
• In the early 1900’s Carrel & his associates made investigations with
the scientific approach to wound healing. Later Carrel (1916), Harvey
& Howe’s (1930), studied incised wounds & contributed to the
knowledge of wound healing.
• There is a saying; “If there were no regeneration, there would be no
life; if everything regenerated, then, there would be no death”.
• The earliest medical writings deal extensively with wound care. Seven
of the 48 case reports included in the Edwin Smith Papyrus (1700 BC)
describe wounds and their management.
• Empirically, in Egypt, Greece, India and Europe, the physicians
developed gentle methods of treating wounds by removing foreign
bodies, suturing, covering wounds with clean materials, and
protecting injured tissues from corrosive agents
9
• More than 4000 years ago, the theory of the "three healing gestures"
was formed, with earliest writing recorded on a clay tablet from 2200
BC.
• wound washing
• application of bandage over the wound
• These gestures evolving into varying forms of today’s same basic
themes. The Greeks belief of dry healing came from Hippocrates, at a
time when the only function of dressings was thought to be the
protection of the wound from injury.
• During the fourteenth century, with the widespread use of gunpowder
and the increasing frequency of bullet wounds, there was an increased
need for surgeons assuming an aggressive posture, which was often
done at the expense of aseptic precautions. Examples included
applications of burning oil, scalding water, wine, turpentine, feathers,
sugar, clay, bismuth, milk of magnesia to wounds. However, none of
these have proven efficacy leased on sound scientific studies.
• The modern era of gentle wound care started in the mid-sixteenth
century, when Ambroise Pare, the great French army surgeon, who
during the Battle of Villaine, applied milder agents like digestive
10
solution of egg yolk, rose oil, honey and turpentine to amputation
stumps with dramatic results.
• John Hunter, William Stewart Halsted, Alexis Carrel and many other
great clinical biologists demonstrated that minimizing tissue injury
produces rapid and effective healing leading to the "minimal
interference" concept of wound care. If the surgeon can remove all
impediments, normal wound healing process will produce the best
possible result.
• Joseph Lister advocated cleanliness in the hospital, the frequent use of
soap and water on wounds and carbolic acid dressings of contaminated
wounds. Later Semmelweis, Ehrlich, Fleming, and Florey also
realized that bacteria were pathogens. Control of bacteria by asepsis,
antiseptics and antimicrobials heralded a new era in wound
management.
• Finally it is apt to say that advances of the previous decades are only
a prelude to the changes in wound care management that will occur in
the coming decades.
Acute wounds are a common health problem. Typically, acute wound
healing is a well-organized process leading to predictable tissue repair where
platelets, keratinocytes, immune surveillance cells, microvascular cells, and
fibroblasts play key roles in the restoration of tissue integrity. The wound repair
process can be divided into 4 temporarily and spatially overlapping phases:
coagulation, inflammation, formation of granulation tissue (proliferative phase),
and remodelling or scar formation phase (figure 1).
12
MECHANISMS OF NORMAL WOUND HEALING:
Normal wound healing processes can be divided into 4 overlapping phases:
coagulation (not shown), inflammatory phase (A), proliferative phase/granulation
tissue formation (B), and remodelling phase (C).
Immediately after injury, platelets adhere to damaged blood vessels,
initiate a release reaction, and begin a haemostatic reaction, giving rise to a blood-
clotting cascade that prevents excessive bleeding and provides provisional
protection for the wounded area (FIGURE 1). As has been well studied, blood
platelets release well over a dozen growth factors, cytokines, and other survival
or apoptosis-inducing agents. Key components of the platelet release reaction
include platelet-derived growth factor (PDGF) and transforming growth factors
A1 and 2 (TGF-A1 and TGF-2), which attract inflammatory cells, such as
leukocytes, neutrophils, and macrophages. As leukocytes are phagocytic cells,
they release reactive oxygen species (ROS) that are antimicrobial and proteases
that clear the wound of foreign bodies and bacteria. Resolution of the
inflammatory phase is accompanied by apoptosis of inflammatory cells, which
occurs gradually within a few days after wounding. The mechanism for resolution
of inflammation is currently unknown. However, studies suggest that anti-
inflammatory cytokines, such as TGF-A1 and interleukin 1, and bioactive lipids,
such as cyclopentenone prostaglandin, lipoxins, and resolvins, take part in this
process. The exact role of these entities during inflammatory phase resolution is
under investigation.
As the inflammatory phase subsides, the proliferative phase of repair
begins. At this stage, growth factors produced by remaining inflammatory cells
and migrating epidermal and dermal cells act in autocrine, paracrine, and
juxtacrine fashion to induce and maintain cellular proliferation while initiating
cellular migration; all these events are required for the formation of granulation
tissue while supporting epithelialization. As dermal and epidermal cells migrate
and proliferate within the wound bed, there is a frank requirement for an adequate
blood supply for nutrient delivery, gas, and metabolite exchange. Therefore, for
wound healing to progress normally, a robust angiogenic response must be
initiated and sustained.
hypoxia, secondary to injury-induced blood vessel disruption, occurs. This event
fosters the production of proangiogenic factors. Vascular endothelial growth
factor (VEGF), fibroblast growth factor 2 (FGF-2), and PDGF, initially released
by platelets and then by resident cells within the wound bed, are all central
mediators of injury-induced angiogenic induction. In response, endothelial cells
degrade basement membrane, migrate toward the wound site, proliferate, and
form cell-cell contacts and eventually new blood vessels. More recently, it has
been revealed that endothelial progenitor cells (EPCs) are also required for wound
revascularization. Normally, EPCs reside in the bone marrow and are recruited
15
into the circulation in response to injury. Subsequently, EPCs are engrafted into
the remodeling microvasculature, taking residence adjacent to endothelial cells
bordering the injury site. Endothelial progenitor cell mobilization is mediated by
nitric oxide, VEGF, and matrix metalloproteinases (MMP), particularly MMP-9;
EPC engraftment and possibly differentiation occur in response to stomal cell–
derived factor 1 and, as has become apparent more recently, insulin like growth
factor (IGF). Although more research needs to be done to further elucidate the
mechanisms of EPC recruitment and homing, it is clear that these progenitor cells
are necessary for normal wound healing– associated neovasculogenesis and
injury repair. In fact, key signalling intermediates responsible for
coordinating/regulating wound healing angiogenesis and vasculogenesis may be
dysfunctional during diabetes. Indeed, diabetic patients prone to the development
of chronic wounds may exhibit deficiencies in either EPC bone marrow release
or peripheral tissue homing and engraftment. Thus, therapies aimed at correcting
EPC-linked deficiencies may prove beneficial for treating diabetes-induced
chronic wounds.
Reestablishment of a normal blood supply provides a favourable
microenvironment for epidermal and dermal cell migration and proliferation. In
turn, this leads to wound re-epithelialization and restoration of epidermal
integrity. Fibroblasts proliferate within the wound and synthesize extra-cellular
matrix (ECM) forming granulation tissue perfused with newly formed blood
vessels. Simultaneously, provisional matrix mainly consisting of collagen III,
fibrin, fibronectin, and hyaluronic acid is progressively substituted with ECM
mainly containing collagen I. Next, wound contraction and matrix remodelling
occur. Contraction is mainly achieved by differentiated fibroblasts or
myofibroblasts that, in response to TGF-A, tissue tension, and the presence of
certain matrix proteins (such as ED-A fibronectin and tenascin C), acquire
smooth muscle actin–containing stress fibres. Fibroblast-induced contractile
forces are then transmitted to the ECM via cytoskeleton-associated and ECM
receptor–dependent mechanocoupling focal adhesion complexes, that is, integrin
receptors. Another mechanism leading to wound contraction is fibroblast motility
with consequent matrix reorganization. This dynamic and reciprocal process
involves slow cycles of ECM synthesis and degradation both occurring in a
stromal- or fibroblastic cell–dependent manner. Here, matrix-remodelling
enzymes, particularly MMPs, play important roles in remodelling the local matrix
microenvironment in support of several healing responses, including cellular
17
migration, proliferation, and angiogenic induction. Finally, apoptosis of
fibroblastic cells occurs, leading to the formation of a relatively acellular scar
tissue whose tensile strength is comparable with unwounded skin.
Although the importance of apoptosis in granulation tissue remodelling and scar
formation is widely accepted, the triggers of apoptosis are not well understood. It
has been suggested that TGF-A, tumour necrosis factor, and surprisingly FGF-2
(that normally is considered a stimulator of cell proliferation) can lead to an
increase in the number of apoptotic cells during the final phase of healing.
Inability of dermal cells, particularly myofibroblasts to undergo timely apoptosis,
has been linked to wound healing pathologies, including the hypertrophic scar
and keloid formation. Clinicians’ improved understanding of the role of apoptosis
in normal and pathological wound healing may initiate novel approaches for their
treatment and/or prevention.
CHRONIC WOUNDS:
The majority of the chronic wounds begin as minor traumatic injuries.
penetrating injuries, insect bites, or even simple scratches of dry skin that would
normally heal within a few days/weeks can lead to formation of a nonhealing
wound in patients with underlying pathologies, such as diabetes-induced and
nondiabetic neuropathies.
Chronic wounds can be classified into vascular ulcers (e.g., venous and
arterial ulcers), diabetic ulcers, and pressure ulcers. Some common features
shared by each of these include a prolonged or excessive inflammatory
phase, persistent infections, formation of drug-resistant microbial biofilms, and
the inability of dermal and/or epidermal cells to respond to reparative stimuli. In
aggregate, these pathophysiologic phenomena result in the failure of these
wounds to heal. The underlying pathologies, however, deviate in different types
of chronic wounds.
Microenvironment within a normal wound bed (left) is characterized by
the presence of numerous growth factors, a well-organized ECM, and responsive
cell populations. Matrix synthesis, here, exceeds its degradation, and MMP
activity is regulated by the presence of MMP inhibitors (TIMPs). Angiogenesis
and neovascularization of normal wounds proceed in a timely manner via well-
regulated sprouting of existing blood vessels and recruitment of endothelial
progenitor cells (EPC), respectively.
Finally, unlike their chronic counterparts, acute wounds are generally
characterized by low bacterial burden. Chronic wounds (right) often have high
incidence of bacterial biofilms, leading to persistent inflammation, excessive
proteolysis, and degradation of critical growth factors, receptors, and/or ECM.
Cells residing within these wounds are unable to proliferate and/or migrate
effectively perhaps because of the absence of functional receptors or appropriate
promigratory matrix substrates. Impaired angiogenesis and neovascularization,
both hallmarks of chronic wounds, result in insufficient oxygen and nutrient
supply for the cells residing within the wound bed, which leads to further wound
bed mutilation and impaired healing.
VENOUS ULCERS:
Venous ulcers display profound pathological changes that arise secondary
to venous valvular incompetence in the deep and superficial veins. This, in turn,
leads to a constant blood backflow resulting in an increase in venous pressure.
Pressure-induced changes in blood vessel wall permeability then lead to leakage
of fibrin and other plasma components into the perivascular space. Accumulation
of fibrin has direct and negative effects on wound healing. It down-regulates
collagen synthesis, leads to formation of pericapillary fibrin cuffs that create a
barrier for normal vessel function, and traps blood-derived growth factors, In the
1980s and 1990s, the cuffs were considered as continuous obstructions preventing
free blood-dermis oxygen exchange. Recently, however, using confocal
21
microscopy, it has been demonstrated that fibrin deposits surrounding dermal
veins are patch like and discontinuous. These findings question the barrier role of
fibrin cuffs and suggests the presence of yet other unknown factors contributing
to low oxygen tension found in venous ulcers and surrounding tissues.
Identification of these factors may reveal novel targets for therapeutic
interventions and treatment of venous ulcers.
ARTERIAL ULCERS:
Arterial ulcers are less common than chronic venous wounds. They occur
because of arterial insufficiency caused by atherosclerosis or embolism that can
lead to narrowing of arterial lumen and ischemia, which prevents timely healing
of minor traumatic injuries. Unlike venous ulcers, which generally arise between
the knee and the ankle, arterial leg wounds may present at any spot distal to
arterial perfusion such as a tip of a toe. Unlike venous ulcers that often can be
improved with therapeutic compression, chronic wounds linked to arterial
insufficiency can be treated successfully only after the restoration of arterial
function via revascularization. Current options for limb revascularization are
rather limited and include reconstructive surgery (angioplasty) or pharmaceutical
interventions. Because failure of wound revascularization almost inevitably leads
to limb amputation in arterial ulcer sufferers, novel techniques allowing for
restoration of blood supply to the wound bed, including stem cell therapies, are
now under investigation.
PRESSURE ULCERS:
Pressure ulcers develop as a result of prolonged unrelieved pressure and
shearing force applied to skin and the underlying muscle tissue leading to a
decrease in oxygen tension, ischemia reperfusion injury, and tissue necrosis.
Pressure ulcers are common in patients with compromised mobility and
decreased sensory perception (neuropathies) and are exacerbated in individuals
with arterial and venous insufficiencies described above.
DIBAETES MELLITUS:
Complications of aging and diabetes can lead to and exacerbate vascular
pathologies related to both arterial and venous insufficiencies and worsen
pressure ulcers. Other abnormalities leading to development of chronic wounds
in diabetic patients (also called diabetic ulcers) include neuropathy, often linked
to vascular impairment, deficiencies in muscle metabolism, and a number of
microvascular pathologies often caused by hyperglycaemia. Macroscopic
pathologies seen in chronic, particularly diabetic, wounds often are linked to
cellular phenotypic abnormalities, including low mitogenic potential and inability
to respond to environmental cues. Thus, a better understanding of these cellular
changes may aid in the development of better treatment options.
Although all of the wounds described previously may have different
origins, each wound is characterized by a chronically inflamed wound bed and a
failure to heal. Excessive recruitment of inflammatory cells to the wound bed
23
often triggered by infection and cell extravasation is facilitated by
disproportionate expression of vascular cell adhesion molecule 1 and interstitial
cell adhesion molecule 1 by resident endothelial cells. Inflammatory cells
accumulated inside the chronic wound produce various ROS that damage
structural elements of the ECM and cell membranes and lead to premature cell
senescence. In addition to these direct negative effects, ROS together with
proinflammatory cytokines induce production of serine proteinases and MMPs
that degrade and inactivate components of the ECM and growth factors necessary
for normal cell function. Inactivation of proteinase inhibitors by proteolytic
degradation augments this process. Therefore, although the production of growth
factors is often increased in chronic compared with acute wounds, their quantity
and bio-availability are significantly decreased.
Figure 4
senescence/apoptosis are all elevated in chronic wounds. These processes cannot
be overcome because of insufficient levels of cell proliferation, ECM synthesis,
production of TIMPs, and impaired angiogenesis/ neovascularization. This
imbalance leads to inability of chronic wounds to heal.
FIGURE 5
perturbed or disequilibrated during chronic wound healing.
Low density growth factor receptors and low mitogenic potential
The phenotypic abnormalities of epidermis- and dermis-derived cells
residing in chronic wounds include lower density of growth factor receptors and
lower mitogenic potential preventing them from responding properly to
environmental cues. For instance, fibroblasts, isolated from patients with chronic
diabetic, chronic nondiabetic wounds, or patients with venous insufficiency, have
lower mitogenic response to PDGF-AB, IGF, bFGF, and epidermal growth factor
applied separately or in combination. These findings are likely due to a decrease
in receptor density. Furthermore, fibroblasts isolated from leptin receptor–
deficient diabetic mice, as well as derived from patients with chronic venous
insufficiency, have reduced motility, compared with normal fibroblasts. These
cellular abnormalities impede the formation of granulation tissue and ECM
deposition, leading to formation of nonhealing wounds.
Impaired keratinocytes
Keratinocytes derived from chronic ulcers have also been reported to possess
a “chronic wound–associated” phenotype. Overexpressing the proliferation
marker Ki67, these cells up-regulate expression of several cell cycle–associated
genes, such as CDC2 and cyclin B1, suggesting a hyperproliferative
status. However, these chronic wound–derived keratinocytes exhibit impaired
migratory potential. The mechanisms of this impairment are not completely
26
understood but have been linked to decreased production of laminin 332
(formerly known as laminin 5), which is an important epithelial ECM component
and substrate for injury-induced keratinocyte migration. In addition, these cells
possess an increased activation of A-catenin/c-myc pathway and do not express
markers of differentiation, particularly keratin 10 and keratin 2.
Growth factors dysregulation
Finally, several genes encoding a variety of growth factors are down- or
up-regulated; for example, VEGF, epiregulin, and TGF-A2 expression are
decreased, whereas PDGF and platelet-derived endothelial growth factor
encoding genes are up-regulated. Decreased growth factor production directly
confirms the impaired state of the keratinocytes residing within a chronic wound
and inability to fully participate in repair processes, whereas up-regulation of key
growth factor genes enables a sustained proliferative capacity, suggesting that
this could be an “entry point” for therapeutic intervention.
Mitogenic stimuli together with activators of keratinocyte differentiation,
such as recently described hyperforin, may be able to induce phenotypic changes
and transform the chronic wound keratinocytes into competent cells necessary for
epithelialization. Similarly, modern transduction techniques could be used to
improve growth factor responsiveness of cells residing in chronic wounds by
increasing the density of growth factor receptors.
27
CONTRIBUTE TO SUSTAINING WOUND CHRONICITY:
The microenvironment of the chronic wound bed is heralded by a matrix.
It is known, however, that deposition of a number of matrix components is
different in chronic as compared with acute wounds.
- Chronic wounds are characterized by prolonged or insufficient
expression of fibronectin, chondroitin sulphate, and tenascin, which
gives rise to impaired cellular proliferation and migration.
- Reduced production of laminin 332—a basement membrane
component that serves as a chemotactic substrate for postinjury
keratinocyte motility was found to be one of the reasons for impaired
reepithelialisation and wound healing.
structural components, can also negatively influence cellular responses
to injury.
- Matrix glycation is often seen in diabetic patients and is likely to be
responsible for or linked to premature cell senescence, apoptosis,
inhibition of cell proliferation, migration, and angiogenic sprout
formation.
- Glycation adds to matrix instability and disrupts matrix assembly and
interactions between collagen and its binding partners, including
heparan sulphate proteoglycans.
28
- High glucose has also been shown to stimulate MMP production by
fibroblasts, macrophages, and endothelial cells, thus contributing to a
“vicious” cycle of matrix degradation detrimental for cell survival and
therefore wound healing.
intermolecular cross-linking seen under hypoxic conditions and
excessive matrix degradation by MMPs are also detrimental to the
healing process.
for cell survival and function and, ultimately, injury repair. Therefore,
inhibition of matrix degradation, addition of exogenous matrices, and
induction of matrix synthesis by resident cells all provide therapeutic
opportunities.
BIOFILMS AND CHRONIC WOUND BED:
Infection is an extrinsic factor that causes delay of wound healing,
contributing to wound chronicity, morbidity, and mortality. High bacterial counts
of greater than 105 viable bacteria or any number of A-haemolytic streptococci
are considered detrimental. Bacterial toxins (as well as live bacteria) induce
excessive inflammatory responses and tissue damage that can lead to abscess,
cellulites, osteomyelitis, or limb loss (diabetic patients). Furthermore, recruited
inflammatory cells, as well as bacteria, produce a number of proteases (including
29
MMPs), which degrade the ECM and growth factors present within the wound
bed. Bacteria that colonize chronic wounds often form polymicrobial
communities called biofilms. These complex structures are composed of
microbial cells embedded in secreted polymer matrix, which provides optimal
environment for bacterial cell survival, enabling their escape from host immune
surveillance/defence and resistance to antibiotic treatment. Although biofilms are
prevalent in chronic wounds and significantly delay re-epithelialization in animal
models, it remains unclear precisely how they delay healing. Increased bacterial
survival and enhanced production of virulence factors are likely explanations.
Nonetheless, it is possible that extracellular biofilm components possess or
display a toxic phenotype for host cell functionality and therefore impede healing.
Recently, it has been demonstrated that hindering biofilm formation by RNAIII-
inhibiting peptide reverses wound-healing delays induced by bacterial
biofilms. Better understanding of the precise mechanisms by which bacterial
biofilms delay repair processes together with optimizing methods for biofilm
detection and prevention may enhance opportunities for chronic wound beds to
actively heal
Most wounds do not require extensive debridement, yet the principles
must always be remembered. Dressings are used to serve the following
purposes.
Promote proper wound healing
1. Sterile debridement set containing
Sharp scissors
Smooth forceps
5. Medicines - Povidone iodine 2.5% - Bactericidal
Dakin's solution (chlorazene 0.25%)
Vaseline gauze
Normal saline
Dakin's solution: is a chlorine releasing agent that is both bactericidal and
active in loosening necrotic tissue to aid in local debridement. Dakin's also
helps to control fetid odours from severely infected wounds.
Routine Foot Dressings:
o Moisten gauze with appropriate solution and pack the wound
gently.
o Fashion a heel cup from cut, folded and taped abdominal pad.
o Fluff two 4 inch gauze sponges over toes.
o Secure the primary dressing, including heel cup by using a
spiral roller by wrapping in a figure of eight fashion.
o Apply paper tape to secure the roller gauze.
Casts / Splints:
A cast or splint may be applied to immobilize a limb after a skin graft
or to protect the incision and reduce contractures after a below knee
amputation. Applying a rigid plaster cast or splint to any neuropathic
extremity can be hazardous and may cause pressure sores.
32
Amputation Stump Dressings:
The dressing applied to any amputation stump is fashioned to meet the
needs of the wound. Since most amputation wounds do not have drains, the
dressing is put on more for wound protection than to collect and contain
blood and secretions. A first trans metatarsal amputation dressing is a bulky
standard foot dressing. A posterior splint may be applied to prevent plantar
flexion and thus avoid tension on the delicate suture line. A below knee
amputation (BKA) requires an extra bulky initial.
Dressing to contain the initial expected bleeding. Below knee
amputations are managed with a posterior splint that extends from the crease
of the buttocks to beyond the end of the stump. A well-padded knee
immobilizer is the splint of choice. Knee flexion is a natural pain-relieving
action or reflex that, if allowed to occur, can lead to serious contracture. It is
customary to have a patient with a BKA measured for a prosthesis on the 3rd
or 4th post op day. Depending on the progression of stump healing, a patella
bearing prosthesis may be fitted and patient begins mobilization eight to ten
days postoperatively.
The initial dressing for an Above Knee Amputation (AKA) is bulky
and similar to the BKA dressing. Splints are not used for AKA despite the
tendency for patients to hold up and flex the painful thigh. The stump usually
33
falls down with muscle fatigue, thus decreasing the tendency for a hip
contracture.
Skin graft dressings are usually applied in accordance with the
surgeon's preference. Mesh grafts are the most common split thickness skin
graft. The mesh graft has proved to be the most successful because the open
mesh allows adequate wound drainage.
Bed rest is the first thing in the care of a diabetic foot lesion. Bed rest
must be absolute and continuous. A patient with diminished circulation who
has a painful ischemic foot lesion may be helped by having the head of the
bed elevated to 6-8 inches. This elevation allows gravity flow of blood to the
feet and is known as arterial position or Reverse Trendelenburg position.
34
1. Growth Factors
Greater understanding of the healing process at the cellular level has
resulted in the use of growth factors like becaplermin, recombinant platelet-
derived growth factor, are produced through recombinant DNA technology.
According to a study by Steed et al, debridement enhances the effectiveness
of becaplermin in healing chronic neuropathic ulcers.
2. Human Skin Equivalents
Modern human skin replacement dates back to the 1960s, when
advances in tissue culture technologies led to the cultivation of human
epidermal cells. These were obtained via biopsy of the tissue and treated with
trypsin so that the dermis gets separated from epidermis.
The keratinocytes were then grown in vitro to produce sheets of
autologous epidermal tissue. These sheets were fragile, delicate to handle,
and provided only 50 percent to 60 percent permanent take. New tissue
required two to three weeks growth time, and lacked a dermal component,
vital in skin grafting.
More dermis grafted means less wound contracture and scarring, more
tensile strength and better cosmetic results. Refinements in the development
of a matrix led to the development of Dermagraft, a living, metabolically
active, immunologically inert dermal tissue.
35
Dermagraft contains normal dermal matrix proteins and cytokines,
and is composed of cultural neonatal fibroblasts grown on a polyglycolic acid
bioabsorbable mesh. As the tissue grows it produces extracellular proteins
and closely resembles human skin. In two studies by Gentzkow et al and one
by Pollak et al, patients were enrolled with full-thickness diabetic ulcers that
had adequate perfusion. Pooled data showed that 51 percent of those who
received a weekly application of Dermagraft for 12 weeks achieved complete
healing, vs. 31.7 percent in the control group.
Apligraf, another living tissue equivalent, was approved by the Food
and Drug Administration in 1998 for venous leg ulcers. Apligraf consists of
bovine Collagen matrix containing fibroblasts and connected to a layer of
stratified epithelium. The result is a sheet of tissue with both dermal and
epidermal layers, metabolically and biochemically comparable to human
skin. The dermo epidermal junction is flatter, however, and there are no
melanocytes, Langerhans cells, lymphocytes or hair follicles present.
In a study by Falanga et al, 293 patients with non-healing venous
ulcers received either compression therapy or Apligraf. At six months, 63
percent of the patients receiving Apligraf healed vs. 49 percent in the control
group and did I so more quickly - than the control group - 61 vs. 181 days to
closure.
36
3. Miscellaneous Topical Agent:
Collagen: Collagen is critical in the proliferative phase of wound healing.
Exogenous sources of collagen primarily purified bovine extracts, are
available as gels, particles, and in an alginate dressing. Exogenous collagen
provides additional protein for tissue repair. As a foreign agent it might also
revert the chronic wound to an inflammatory phase, "jump-starting" the
healing process.
Donaghue et al evaluated the alginate dressing (Fibracol, Johnson and
Johnson, Arlington, Texas) in the treatment of diabetic foot ulcers. Seventy-
five patients were randomly assigned to either a collagen-alginate dressing
or gauze group. At the end of the study, the mean reduction in wound size
was 80.6 percent for the collagen-alginate group and 61.1 percent for the
gauze group. Complete healing was achieved in 48 percent of the collagen-
alginate group and 36 percent in the gauze group.
Hyaluronic Acid: Hyaluronic acid is involved in the structure and
organization of the extracellular matrix and is associated with increased
mitotic activity. It is a highmolecular weight polysaccharide synthesized in
the plasma membrane of fibroblasts and other cells. The ability of injured
fetal tissues, which are high in Hyaluronic acid, to heal without scarring has
prompted extensive research
37
Beta Glucan: It is a major cell-wall carbohydrate extracted from such grains
as oats and barley. The biological activity of beta glucan results from its
ability to bind macrophage beta-glucan receptors and promote macrophage
stimulation.
Beta glucan products enhance the activities of not only macrophages
but also neutrophils, natural killer cells, T cells and B cells. Beta glucan is
thought to increase macrophage infiltration, speeding the onset of fibroplasia
and fibrogenesis, stimulation of increased tissue granulation, and enhanced
reepithelialisation. Beta glucan is available as either BCG matrix or Glucan
II.
Both are available in multifilament mesh dressings; BCG matrix is
also impregnated with collagen.
promoting healing. Arglaes is an inorganic phosphate similar to other
compounds such as silver nitrate, silver oxide and silver chloride. It consists
of fused sodium and calcium phosphates with small amounts of silver in the
presence of water, these materials release free silver ions.
4. Pharmaceuticals:
Oxandrolone: Oxandrolone is an anabolic steroid with a high anabolic and
low androgenic ratio, and has anticatabolic, protein-sparing properties.
Exogenous anabolic agents clubbed with nutritional intervention can result
38
in a threefold to fourfold higher rate of protein synthesis than with nutritional
interventions alone.
Demling and De Santi studied eight patients with non-healing wounds
and a 10 percent or greater loss of body weight. Nutrition was optimized over
four weeks, without significant effect on weight gain or healing. Adding
oxandrolone resulted in gains of approximately 4 pounds per week across 12
weeks. During this time, five wounds closed completely and three others
were 75 percent closed.
intermittent negative pressure at 125 mmHg promoted wound healing by
improving blood flow, granulation tissue growth rates and nutrient flow
while reducing bacterial levels. Based on these findings, Kinetic Concepts
(San Antonio, Texas) developed the VAC system. The VAC consists of a
wound dressing (a charcoal - impregnated sponge - like material) connected
by tubing to a wound canister, with a pump that creates negative pressure. A
transparent drape or film over the dressing establishes the seal needed to
create a vacuum. The pump can be adjusted for various levels of intermittent
or continuous pressure. Exudate is collected in the cainster. The VAC also is
said to reduce edema.15
Radiant Heat Bandage: Heat therapy has long been employed, especially
for musculoskeletal conditions, but it has not been widely used as a wound
healing modality. Heat increases local blood flow, subcutaneous oxygen
tenson which improve healing mechanisms. In clinical studies by Santilli and
Robinson on patients with venous leg ulcers, those who used radiant heat
bandage devices reported significant decreases in both wound size and pain
across two weeks with no adverse effects.16
Topical Hyperbaric Oxygen Therapy:
The therapy is based on achieving an atmospheric pressure of 1.02 to
1.03 atmos, which is thought to stimulate fibroblast, growth, collagen
formation and neoangiogenesis. This provides a lethal environment for
anaerobes, often a normal part of the diabetic foot's flora. Topical hyperbaric
oxygen is administered using a sealed polyethylene bag over the affected
area and administering 100 percent oxygen to a pressure between 20 and 30
mmHg. Treatments last 2 to 2 and a half hours.
In a study of Landau, 50 patients with diabetic ulcers were treated with
topical hyperbaric therapy, alone or with a low-energy laser. On average, 25
treatments were performed over three months. Forty-three of the 50 patients
experienced resolution of their ulcers.
40
Classification of Dressings:
Wound dressings have evolved over the years on the principles of
providing protection to wound raw surface, absorbing exudates, controlling
infection and promoting granulation tissue formation and creating ideal
environment for healing.
1. Short term application: we should replace these dressings frequently
2. Long term or skin substitutes:
Temporary: these are applied till complete healing. Used in partial
thickness wounds
thickness wounds.
material used for preparation. Each further divided into:
o Primary Dressing : Which is in physical contact to the wound bed.
o Secondary Dressing : Primary dressings are covered with these
dressings.
o Island Dressing : at the central region there is absorbent part, adhesive
part surrounds the central portion.
41
A. Conventional Dressings:
Fabric materials like gauze are used, but these allows moisture to
evaporate and dries the desiccated wound bed.Also causes exogenous
bacteria to enter the wound. Some used paraffin soaked dressings. This also
led to development of usage of antibacterial agents like polymixin,carbolic
acid in combination with dressings.
B. Synthetic Dressings:
1. Films: these are polymer sheets with adhesive coated on one side.
Polyurethane, polyethylene, dimethyl aminoethyl methacrylate, polytetra
fluoroethylene are commonly used in superficial wounds. But causes
accumulation of wound fluid, due to impermeability to water vapour and
gases, and lack of absorbing capacity. Thus, leading to leakage and entry of
exogenous bacteria.
2. Foams and sprays: Polymers of polyvinyl alcohol and polyurethane
are converted to foam solutions and are used for dressings. They are better
than film dressings. They provide thermal insulation and keep the surface
moist. They are permeable to gas. They are non-adherent also. Silastic foam
and lyofoam are examples. Spray dressings are co polymers of certain
compounds, eg: hydroxyl vinyl chloride acetate modified maleic acid ester
is polymerised to form Aeroplast.
42
3. Composite dressings: This dressing consists of more than one layer.
Durability and elasticity maintained by outer layer. And inner layer
maintains the adherence.
a. Hydrocolloid dressings: These contain mixture of gelling agents and
elastomeric adhesive. Commonly used absorptive agent is Carboxymethyl
cellulose.
b. Hydrogel sheets: These are hydrophilic polymers made into sheets of 3
dimensional networks. Polyethylene oxide, polyacrylamide and
polyvinyl pyrrolidine are usually used in thermal burns because of their
cooling ability.
Eg: Vigilon.
c. Hydrogel Amorphous: They are similar to hydrogel, but there isn’t any
crosslinking between the polymers. Collagen or complex carbohydrates
are present in small amounts. They give moisture to dry wound eschar and
also promotes autolytic debridement
e. Gels: examples are HEMA, Hydran, Geliperm etc.
Above mentioned dressing is usually act as a temporary covering. In
large burns injuries these are combined with alternative wound closure
techniques.
43
They are obtained naturally from tissues and are combined with
collagen lipid and elastin in various formulations. Their main advantages
over synthetic dressings are:
1. Prevent dehydration of wound by restoring a water vapour barrier.
2. Lessen heat loss by evaporation
3. Exudative loss of protein and electrolytes are reduced.
4. Contamination of wound by organism are prevented.
5. Change of dressings are less painful.
6. Joint mobility is maintained.
7. Wound debridement can be done.
8. Autografting made easy by creating good granulation.
9. Reduce the healing time and
10. Healing quality is improved and contraction of tissues are decreased.
Other Biological dressings which are used are allografts,embryonic
membranes, skin of foetus/neonate, fibrin, grafts from cultured
epidermis/dermal matrix, bovine collagen is reconstituted to films.
Heterografts from pigs and dogs are also used.
44
COLLAGEN
Proteins are natural polymers and make up almost 15% of the human body. The
building blocks of all proteins are amino acids. Collagen is the major protein of
the extracellular matrix (ECM) and is the most abundant protein found in
mammals, comprising 25% of the total protein and 70% to 80% of skin (dry
weight). Collagen acts as a structural scaffold in tissues. The central feature of all
collagen molecules is their stiff, triple-stranded helical structure. Types I, II, and
III are the main types of collagen found in connective tissue and constitute 90%
of all collagen in the body. Function of collagen in wound healing. Previously,
collagens were thought to function only as a structural support; however, it is now
evident that collagen and collagen-derived fragments control many cellular
functions, including cell shape and differentiation, migration, and synthesis of a
number of proteins.
ROLE OF COLLAGEN IN WOUND HEALING:
Type I collagen is the most abundant structural component of the dermal
matrix; migrating keratinocytes likely interact with this protein. Collagenase
(via formation of gelatin) may aid in dissociating keratinocytes from collagen-
rich matrix and thereby promote efficient migration over the dermal and
provisional matrices. Cellular functions are regulated by the ECM. The
information provided by ECM macromolecules is processed and transduced
into the cells by specialized cell surface receptors. Evidence demonstrates that
the receptors play a major function in contraction of wounds, migration of
epithelial cells, collagen deposition, and induction of matrix-degrading
collagenase. Although keratinocytes will adhere to denatured collagen
(gelatin), collagenase production is not turned on in response to this
substrate. Keratinocytes have been known to recognize and migrate on Type I
collagen substratum, resulting in enhanced collagenase production.
Collagen plays a key role in each phase of wound healing.
Platelets aggregate around exposed collagen. Platelets then secrete factors,
which interact with and stimulate the intrinsic clotting cascade, which
strengthens the platelet aggregate into a stable haemostatic “plug.” Blood
platelets also release αa-granules, which release a variety of growth factors
(GFs) and cytokines, such as platelet derived GF (PDGF), insulin-like GF
(IGF-1), epidermal GF (EGF), and transforming GF-beta (TGF-b), which
46
phase. Inflammation (duration = days).
TNF-α and IL-1bβ are key pro-inflammatory cytokines, which directly
influence deposition of collagen in the wound by inducing synthesis of
collagen via fibroblasts and down regulation of tissue inhibitors of matrix
metalloproteinases (TIMPs). Inflammatory cells also secrete growth
factors including TGF-b, TGF-b, bHB-EGF, and bFGF. 12 These GFs
continue to stimulate migration of fibroblasts, epithelial cells and vascular
endothelial cells into the wound. As a result, the cellularity of the wound
increases. This begins the proliferative phase. Proliferation (duration =
weeks).
proliferation. Fibroblasts secrete a variety of GFs (IGF-1, bFGF, TGF-b,
PDGF, and KGF), which guide the formation of the ECM.
The collagen cleavage products also stimulate vascular endothelial cell
proliferation. These cells secrete a variety of GFs (VEGF, βFGF,
PDGF), which promote angiogenesis. With a vascularized ECM,
granulation is achieved.
Collagen cleavage products also stimulate keratinocyte migration and
proliferation. Keratinocytes secrete a variety of GFs and cytokines, such as
TGF-b, TGF-b, and IL-1. As keratinocytes migrate from the edge of the
47
achieved. Remodelling (duration = 1+year).
A balance is reached between the synthesis of new components of the scar
matrix and their degradation by MMPs, such as collagenase, gelatinase,
and stromelysin.
Fibroblasts are the major cell type that synthesizes collagen, elastin, and
proteoglycans. They are also the major source of MMPs and TIMPs. In
addition, they secrete lysyl oxidase, which cross-links components of
the ECM. Angiogenesis ceases and the density of capillaries in the wound
site decreases as the scar matures.
The result is the creation of a stronger scar, though the skin only regains
almost 75% of its original tensile strength.
Wound bed preparation (WBP) can be described as the management of
the wound to accelerate endogenous healing or to facilitate the effectiveness of
other therapeutic measures.
The 4 basic aspects of WBP can be represented by the acronym:
TIME. T = tissue (nonviable or deficient);
I = infection or inflammation;
Focusing on the “E” in TIME, collagen dressings possess properties,
which lend themselves to creating a wound environment favourable to the
migration of cells from the epidermal margin across granulation tissue,
encouraging wound closure.
Due to a number of potential stimuli (local tissue ischemia, bioburden,
necrotic tissue, repeated trauma, etc.), the wound has stalled in the
inflammatory phase contributing to the chronicity of the wound.
As a result of the aforementioned pro-inflammatory stimuli, the wound is
overstimulated and inflammatory cells, such as macrophages, are present in
higher numbers and are more active.
49
In addition, the cells, such as fibroblasts and endothelial cells, are senescent
and unable to function properly as they would in an acute wound.
With the overabundance of macrophages, there is an overabundance of key
pro-inflammatory cytokines, such as TNF-b and IL-1b, secreted by the
macrophages.
These pro-inflammatory cytokines signal the fibroblasts to secrete MMPs, but
due to the overabundance of pro-inflammatory cytokines the fibroblasts
secrete elevated levels of MMPs.
At this level, MMPs not only degrade nonviable collagen, but also viable
collagen laid down by the fibroblasts themselves.
Additionally, the fibroblasts are unable to secrete tissue inhibitors of MMPs
(TIMPs) at an adequate level to control the activity of the MMPs.
In addition, cells in a chronic wound tend to be senescent, thus unable to
communicate with other cells and unable to function properly.
One result of this is a lack of endothelial cell activity slowing the formation of
blood vessels. Without an adequate blood supply, tissue can die and as a result,
there is an increase in wound size.
All of the aforementioned phenomena impede the formation of viable
granulation tissue and thus inhibit re-epithelialization (i.e. wound closure).
50
One of the key contributors to wound chronicity is an overabundance (and/or
activity) of MMPs in the wound; the ability to inhibit or deactivate a number
of excess MMPs may help create an environment more conducive to the
formation of granulation tissue, and eventual wound closure.
51
COLLAGEN BASED WOUND DRESSINGS:
There are a number of different collagen dressings available, which employ
a variety of carriers/combining agents such as gels, pastes, polymers, oxidized
regenerated cellulose (ORC), and ethylene diamine tetraacetic acid (EDTA). The
collagen within these products tends to be derived from bovine, porcine, equine,
or avian sources, which is purified in order to render it nonantigenic. The collagen
in a given collagen dressing can vary in concentration and type. Certain collagen
dressings are comprised of Type I (native) collagen; whereas, other collagen
dressings contain denatured collagen as well. A given collagen dressing may
contain ingredients, such as alginates and cellulose derivatives that can enhance
absorbency, flexibility, and comfort, and help maintain a moist wound
environment. Collagen dressings have a variety of pore sizes and surface areas,
as well. All of these attributes are meant to enhance the wound management
aspects of the dressings. Many collagen dressings contain an antimicrobial agent
to control pathogens within the wound. Collagen dressings typically require a
secondary dressing.
53
They are primarily a type 1 collagen in lyophilised particle form with
Mupirocin USP 2% and Metronidazole IP 1% of specified volumes. It is gamma
sterilised and supplied in convenient cold blister packs. Should be stored dry in
at least 25 deg celcius and do not freeze. Shelf life is 2 years.
54
55
56
57
58
RESULTS
The present study comprising of 60 cases of chronic wounds was studied during
a period of May 2018 To May 2019. Both outpatient and inpatients were
diagnosed and included in the study. Patients were categorised into two groups
based on the collagen application and normal dressing. Above mentioned
parameters were assessed and the results were estimated.
59
Figure12: depicting the gender distribution among the case and control
group
60
Figure 13: bar diagram demonstrating the age distribution among the case
and control groups.
61
Figure 14: mean wound surface area before applying collagen dressing and
conventional antibiotic dressing
62
Figure 15: Mean wound surface area after regular dressings with collagen
and conventional antibiotic dressing.
63
Figure 16: bar diagram depicting the mean hospital stay of both case and
control group
64
Figure 18: showing the decrease in wound surface area in case group who
received the collagen granule dressing. Mean wound surface area in case group
is 48.03 cm2 before application of dressings and 39.57 after application of
dressings. This indicates significant reduction in the wound surface area.
Wound surface
area (cm2)
Collagen dressing
Before After
65
Figure 19: Showing the reduction in the duration of mean hospital stay among the
case group who received the collagen dressing than the conventional dressing.
The mean hospital stay for case group is 32.10 days and among the control group
is 45.57 days. There is a significant decrease in the mean hospital stay.
Hospital stay(days) Collagen Convention
66
Figure 20: showing the significant decrease in the number of dressings required
before application of SSG to the wound. The mean number of dressings for
collagen group is 5.40 and for the conventional dressing group is 8.20 and there
is a significant decrease in the no of dressings required.
Number of dressings Collagen Convention
Mean 5.40 8.20
SD 0.86 1.77
67
Figure 21: Showing the decrease in the decrease in the duration between the
first dressing and SSG application. The mean duration in the case group is
22.23 and the control group is 36.03, there is a significant decrease in the
duration between the first dressing and the application of SSG
Difference between the
SSG application Collagen Convention
Collagen is a key component of a healing wound.
Due to a number of potential stimuli (local tissue ischemia, bio burden,
necrotic tissue) wounds can stall the inflammatory phase, contributing to
the chronicity of the wound.
One key component of chronic wounds is an elevated level of matrix
metalloproteinases (MMP), at elevated levels MMPs not only degrade
nonviable collagen but also feed on viable collagen.
In addition, fibroblasts in a chronic wound may not secrete tissue
inhibitors of MMPs (TIMPs) at an adequate level to control the activity of
MMPs.
These events prevent the formation of the scaffold needed for cell
migration and ultimately prevent the formation of the extracellular matrix
and granulation tissue.
Collagen granules redress the grievances as following
It acts as a sacrificial substrate for MMPs, MMPs will act upon it.
Collagen breakdown products are chemotactic for a variety of cell
types required for the formation of granulation tissue.
It has the ability to absorb wound exudates and maintain a moist
wound environment.
microorganisms.
microenvironment.
70
CONCLUSION
On the basis of the statistical analysis of our study we come to the
conclusion that antibiotic coated collagen granule dressing is advantageous
than conventional antibiotic dressing in terms of
Decreased wound surface area
Decreased number of dressings required before the application of skin
grafting.
Decreased duration of hospital stay.
71
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82
PROFORMA
BEFORE AFTER
wound surface
area before
ssg
Hospital
stay
1 Natarajan 38 M Left Diabetic foot Htn, Diabetic 36 5 31 31 yes 21 28
2 Manthaiyan 48 M
foot nil 64 6 60 51 yes 25 35
3 Sekar 57 M Ulcer Rt foot Diabetic 29 6 23 23 yes 25 37
4
Mohamed
5 Chinnaraj 28 M
Rt Hand nil 49 6 44 41 yes 25 34
6 Paraman 65 M
Cellulitis with raw
area Rt leg Htn 73 7 62 62 yes 28 42
7 Subbaiya 65 M Ulcer Lt foot Diabetic 67 5 63 61 yes 21 28
8 Selvaraj 50 M Raw area Lt foot Diabetic 47 5 44 42 yes 21 32
9
Senthil
Eswaran 27 M Rt traumatic ulcer nil 84 6 80 71 yes 24 32
10 Chinnan 60 M Lt diabetic foot Diabetic 33 4 28 27 yes 15 22
11 Rajakumar 40 M
12 Kanthavel 59 M
Rt bk amputee with
stump ulcer Diabetic 35 5 31 29 yes 21 42
13 Savithri 42 M Rt raw area foot Diabetic 22 5 19 19 yes 21 30
14 Rani 48 M Raw area Lt foot Htn 29 6 24 24 yes 24 32
15 Arifa beevi 63 F Raw area Rt foot Diabetic 49 5 43 37 yes 22 30
16 muthupandi 28 M Rt traumatic ulcer nil 84 6 74 74 yes 24 32
17 iyyavu 60 M Lt diabetic foot Diabetic 33 4 28 27 yes 15 22
18 Arun 40 M
85
stump ulcer Diabetic 35 4 31 26 yes 21 40
20 Karuppasamy 42 M Rt raw area foot Diabetic 28 5 27 23 yes 22 31
21 Vellaisamy 47 M
Cellulitis with raw
area Rt leg Htn 29 6 24 24 yes 24 32
22 Pothumponnu 62 F Raw area Rt foot Diabetic 52 5 40 40 yes 22 30
23 Muthandi 38 M Left Diabetic foot Htn, Diabetic 36 6 29 29 yes 21 26
24 Ravi 48 M
foot Diabetic 64 5 48 48 yes 25 35
25 Gopi 56 M Ulcer Rt foot Diabetic 29 6 27 21 yes 25 37
26 Pradeep 55 M
27 Sankar 28 M
Rt Hand Diabetic 49 6 41 41 yes 25 36
28 Amalan 67 M Raw area Lt foot Htn 68 7 62 54 yes 28 42
29 Xavier 60 M Ulcer Lt foot Diabetic 67 5 54 53 yes 21 28
30 Muthulakshmi 53 F Raw area Lt foot nil 47 6 42 38 yes 23 34
86
Sl.
Wound
surface
before
conventional
dressing
2 madathiyammal 75 F
foot CKD, Htn 45 10 43 yes 42 51
3 Ainudeen 34 M Ulcer Rt foot Diabetic 24 7 24 yes 32 40
4 Rajendran 80 M Ulcer Rt foot Diabetic 36 6 35 yes 29 38
5 Petchiyammal 60 F Raw area Diabetic 44 8 44 yes 37 47
6 Jakkariya 46 M
7 Nallamuthu 69 M
area nil 24 5 24 yes 20 30
8 Ashok kumar 25 M Raw area Rt leg nil 38 7 37 yes 33 42
9
Moorthy
Nayakkar 85 M Raw area Lt foot diabetic 47 9 47 yes 34 43
10 Gothandapani 60 M Rt Ulcer foot Diabetic 29 7 28 yes 31 42
11 Rajakesavan 60 M Lt diabetic foot Diabetic 56 10 54 yes 44 55
12 Jothi 60 F Ulcer Rt foot Diabetic 34 7 33 yes 34 42
13 Pothumponnu 72 F
let foot nil 47 9 46 yes 37 45
14 Seethalakshmi 70 F Ulcer Lt foot Diabetic 31 8 31 yes 38 46
15 Muthu lakshmi 48 F Ulcer Rt foot Diabetic 37 8 35 yes 38 47
16 Sanjeevi 66 M
foot CKD, Htn 45 8 43 yes 42 51
17 Samy 34 M Raw area Rt leg Diabetic 24 7 24 yes 32 42
87
18 V ivek 78 M Ulcer Rt foot Diabetic 36 6 35 yes 29 38
19 Geetha 56 F Raw area Diabetic 44 8 46 yes 37 47
20 Vadivel 42 M
21 Irulandi 67 M
area nil 24 5 24 yes 20 34
22 Ajithkumar 25 M Raw area Rt leg nil 38 8 38 yes 33 42
23 Karuppanan 81 M Raw area Lt foot diabetic 49 9 46 yes 34 43
24 Muthu 58 M Lt diabetic foot Diabetic 56 11 54 yes 46 55
25 Begam 48 F Ulcer Rt foot Diabetic 34 7 36 yes 34 42
26 Selvalakshmi 57 F
let foot nil 45 9 46 yes 37 45
27 Sarathkumar 68 M Ulcer Lt foot Diabetic 31 9 33 yes 38 48
28 Karuppayee 48 F Ulcer Rt foot nil 39 7 35 yes 40 44
29 Vellaiyammal 51 F Raw area Lt foot Diabetic 34 8 38 yes 38 48
30 Pappathi 73 F
88
89